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Enhancing natural killer cell function with gp41-targeting bispecific antibodies to combat HIV infection.
Ramadoss, Nitya S; Zhao, Nancy Q; Richardson, Barbra A; Grant, Philip M; Kim, Peter S; Blish, Catherine A.
Afiliación
  • Ramadoss NS; Department of Biochemistry.
  • Zhao NQ; Stanford ChEM-H, Stanford University, Stanford, California, USA.
  • Richardson BA; Department of Medicine, Division of Infectious Diseases and Geographic Medicine.
  • Grant PM; Program in Immunology, School of Medicine, Stanford University, Stanford, California.
  • Kim PS; Department of Biostatistics, University of Washington, Seattle, Washington.
  • Blish CA; Department of Medicine, Division of Infectious Diseases and Geographic Medicine.
AIDS ; 34(9): 1313-1323, 2020 07 15.
Article en En | MEDLINE | ID: mdl-32287071
ABSTRACT
OBJECTIVE(S) The aim of this study was to develop and evaluate the activity of bispecific antibodies (bsAbs) to enhance natural killer (NK) cell antibody-dependent cellular cytotoxicity (ADCC) against HIV-infected cells.

DESIGN:

These bsAbs are based on patient-derived antibodies targeting the conserved gp41 stump of HIV Env, and also incorporate a high-affinity single chain variable fragment (scFv) targeting the activating receptor CD16 on NK cells. Overall, we expect the bsAbs to provide increased affinity and avidity over their corresponding mAbs, allowing for improved ADCC activity against Env-expressing target cells.

METHODS:

bsAbs and their corresponding mAbs were expressed in 293T cells and purified. The binding of bsAbs and mAbs to their intended targets was determined using Bio-Layer Interferometry, as well as flow cytometry based binding assays on in-vitro infected cells. The ability of these bsAbs to improve NK cell activity against HIV-infected cells was tested using in-vitro co-culture assays, using flow cytometry and calcein release to analyse NK cell degranulation and target cell killing, respectively.

RESULTS:

The bsAbs-bound gp41 with similar affinity to their corresponding mAbs had increased affinity for CD16. The bsAbs also bound to primary CD4 T cells infected in vitro with two different strains of HIV. In addition, the bsAbs induce increased NK cell degranulation and killing of autologous HIV-infected CD4 T cells.

CONCLUSION:

On the basis of their in-vitro killing efficacy, bsAbs may provide a promising strategy to improve NK-mediated immune targeting of infected cells during HIV infection.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Asesinas Naturales / Anticuerpos Anti-VIH / Proteína gp41 de Envoltorio del VIH / Infecciones por VIH / Anticuerpos Biespecíficos / Citotoxicidad Celular Dependiente de Anticuerpos Límite: Humans Idioma: En Revista: AIDS Asunto de la revista: SINDROME DA IMUNODEFICIENCIA ADQUIRIDA (AIDS) Año: 2020 Tipo del documento: Article

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Asesinas Naturales / Anticuerpos Anti-VIH / Proteína gp41 de Envoltorio del VIH / Infecciones por VIH / Anticuerpos Biespecíficos / Citotoxicidad Celular Dependiente de Anticuerpos Límite: Humans Idioma: En Revista: AIDS Asunto de la revista: SINDROME DA IMUNODEFICIENCIA ADQUIRIDA (AIDS) Año: 2020 Tipo del documento: Article
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